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Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT.
- Source :
-
Nature communications [Nat Commun] 2019 Mar 25; Vol. 10 (1), pp. 1065. Date of Electronic Publication: 2019 Mar 25. - Publication Year :
- 2019
-
Abstract
- The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (T <subscript>SCM</subscript> ) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1 <superscript>+</superscript> Eomes <superscript>+</superscript> T-bet <superscript>-</superscript> ) BM-T <subscript>SCM</subscript> predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.
- Subjects :
- Adult
Antigens, CD genetics
Antigens, CD immunology
Antineoplastic Agents therapeutic use
Bone Marrow Cells immunology
Bone Marrow Cells pathology
CTLA-4 Antigen genetics
CTLA-4 Antigen immunology
Female
Glucocorticoid-Induced TNFR-Related Protein genetics
Glucocorticoid-Induced TNFR-Related Protein immunology
Hepatitis A Virus Cellular Receptor 2 genetics
Hepatitis A Virus Cellular Receptor 2 immunology
Humans
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute pathology
Leukemia, Myeloid, Acute therapy
Male
Middle Aged
Programmed Cell Death 1 Receptor genetics
Programmed Cell Death 1 Receptor immunology
Receptors, KIR genetics
Receptors, KIR immunology
Recurrence
Remission Induction
Retrospective Studies
Signal Transduction
Signaling Lymphocytic Activation Molecule Family genetics
Signaling Lymphocytic Activation Molecule Family immunology
T-Lymphocytes pathology
Transplantation, Homologous
Lymphocyte Activation Gene 3 Protein
Clonal Anergy
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cell Transplantation
Immunologic Memory genetics
Leukemia, Myeloid, Acute immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 30911002
- Full Text :
- https://doi.org/10.1038/s41467-019-08871-1